This application directly addresses PQ13. Can tumors be detected when they are two to three orders of magnitude smaller than those currently detected with in vivo imaging modalities? To date molecular imaging technologies have had limited clinical impact to date for a number of reasons. One of the primary ones is the inadequate contrast specificity of molecular contrast agents due to non-specific agent binding and background signals from tissue. Major increase in detection sensitivity would provide a fundamental change in how we diagnose and treat cancers. In this context, the overarching goal of this project is to develop an ultrasensitive platform technology based on a recent breakthrough we made on magnetomotion-based imaging-contrast enhancement (Nat. Commun. 2010). We have shown improvement of imaging S/N ratio of 3 orders or magnitude in phantoms by incorporating magnetic properties into imaging contrast agents. Through this project, we plan to further develop this innovative and powerful background suppression technique for in vivo tumor imaging and image-guided therapy. We will use photoacoustic imaging as a model, but the innovative concept and algorism can be expanded to virtually any other molecular imaging modalities involving contrast agents. This platform technology is also compatible with future major developments in the field of biomedical imaging, such as development of more specific probes and more sensitive detectors.